Visfatin在油酸诱导的SW872脂肪细胞胰岛素抵抗中的作用

目的探讨Visfatin在油酸诱导的SW872成熟脂肪细胞胰岛素抵抗(IR)中的作用。方法体外培养SW872前脂肪细胞,当细胞完全汇合后,加入0.6mmol·L-1油酸诱导分化48h,此时SW872前脂肪细胞被诱导分化为成熟脂肪细胞,以SW872成熟脂肪细胞为研究对象,采用1.0mmol·L-1油酸诱导SW872成熟脂肪细胞产生IR。将其分为正常对照组(成熟SW872脂肪细胞)和IR组(采用1.0mmol·L-1油酸诱导SW872成熟脂肪细胞产生IR)。采用2-脱氧-[3H]-右旋葡萄糖掺入法检测2组SW872成熟脂肪细胞基础状态(基础状态组)、Visfatin和Insulin刺激状态(Visfatin和Insulin刺激组)下的葡萄糖转运能力。结果1.在正常对照组中,Visfatin和Insulin刺激组SW872成熟脂肪细胞葡萄糖转运率显著增加,分别是基础状态组的1.10倍(P<0.01)和1.34倍(P<0.01)。2.在IR组中,SW872成熟脂肪细胞的葡萄糖转运率均显著下降。与正常对照组比较,Visfatin刺激组和基础状态组的葡萄糖转运率分别减少12.30%(P<0.01)和9.73%(P<0.0...     

急性心肌梗死患者血清内脏脂肪素水平的变化及其临床意义

目的观察急性心肌梗死患者血清内脏脂肪素(简称内脂素)水平变化及其与冠状动脉病变严重程度和心脏功能的关系,并探讨其临床意义。方法选择急诊行经皮冠状动脉介入治疗的急性心肌梗死(AMI)患者作为观察组(AMI组,n=30),其中男性22例,女性8例,平均年龄为54.77±10.09岁,其冠状动脉病变程度根据冠状动脉病变支数及Gensini积分进行评估;另选同期行冠状动脉造影检查正常者作为对照组(n=30),其中男性20例,女性10例,平均年龄为54.07±11.07岁。采用双抗体夹心酶联免疫吸附法检测两组术前及AMI组术后24 h血清内脂素水平;应用心脏超声测量各组左心室射血分数(LVEF)、左心室舒张末期内径(LVEDD)。结果 AMI组各时间点血清内脂素水平(术前:80.82±7.63μg/L,术后24 h:91.96±7.37μg/L)均显著高于对照组(19.32±4.37μg/L),且AMI组术后24 h血清内脂素水平较术前明显升高,差异均有统计学意义(P0.01)。不同冠状动脉病变支数血清内脂素水平分别为:单支:72.85±2.56μg/L,双支:82.24±5.77μg/L,多支:88.22±6.07μg/L;不同冠状动脉狭窄程度血清内脂素水平分别为:轻度:74.58±4.40μg/L,中度:80.13±4.71μg/L,重度:87.57±6.39μg/L;组间比较差异均有统计学意义(P0.05)。与对照组相比,AMI组LVEF明显降低(P0.01),LVEDD无显著差异。AMI组血清内脂素水平与冠状动脉病变支数、冠状动脉病变Gensini积分呈正相关(r=0.754,r=0.672,P0.01),与LVEF呈负相关(r=-0.459,P0.01)。结论血清内脂素水平可以作为推测AMI患者冠状动脉病变严重程度的指标。     

The release of the adipocytokine visfatin is regulated by glucose and insulin

Aims/hypothesis The novel insulin-mimetic adipocytokine visfatin has been linked to the metabolic syndrome, but its regulation has not been characterised to date. Since insulin-mimetic actions of visfatin may be part of the feedback regulation of glucose homeostasis, we hypothesised that visfatin concentrations are influenced by glucose or insulin blood levels in humans.Subjects, materials and methods In this randomised, double-blind, placebo-controlled crossover study, nine healthy male subjects (age 26±6 years) attended three different study days. On each day, systemic glucose concentrations of 5.0, 8.3 and 11.1 mmol/l were attained by stepwise increases in i.v. infusions of glucose, representing fasting and postprandial conditions. Visfatin plasma concentrations were studied during concomitant exogenous hyperinsulinaemia, inhibition of endogenous insulin production by somatostatin infusion, and placebo time control. Additionally, human adipocytes were cultured to study visfatin release and mRNA expression in vitro.Results Glucose concentrations of 8.3 and 11.1 mmol/l increased circulating visfatin from baseline concentrations of 0.5±0.0 ng/ml to 0.9±0.1 and 2.1±0.3 ng/ml, respectively (p<0.01). Glucose-induced elevation of visfatin was prevented by co-infusion of insulin or somatostatin (p<0.05). Cultured subcutaneous and visceral adipocytes released an equivalent amount of visfatin upon glucose-concentration- and time-dependent stimulation. Visfatin secretion involved the phosphatidylinositol 3-kinase (PI3-kinase) and protein kinase B (AKT) pathways. The mRNA expression pattern of visfatin was consistent with this altered protein release.Conclusions/interpretation Circulating visfatin concentrations are increased by hyperglycaemia. This effect is suppressed by exogenous hyperinsulinaemia or somatostatin infusion. Glucose signalling for visfatin release in adipocytes involves the PI3-kinase/AKT pathway.     

2型糖尿病患者内脂素水平与颈动脉内中膜厚度相关

73例2型糖尿病患者,根据颈动脉内中膜厚度(IMT)分为动脉粥样硬化(AS)组和非AS组,测定血浆内脂素水平.结果 显示,2型糖尿病AS组内脂素水平高于非AS组[(44.95±10.14对34.52±9.08)μg/L,P<0.05],均高于对照组[(24.46±7.18)μg/L,均P<0.05],并与IMT、腰臀比、内脏脂肪厚度、空腹胰岛素、胰岛素抵抗指数呈正相关.年龄、病程、HbA_(1c)及内脂素是影响颈动脉IMT的相关因素.     

胆固醇过负荷对脂肪细胞分泌内脂素的影响及其机制

3T3-L1细胞促分化成熟后,分别以酯酰辅酶A胆固醇酯酰转移酶(ACAT)抑制剂(2μg/ml)和不同浓度(0、25、50、75和100 μg/ml)的氧化型低密度脂蛋白(ox-LDL)干预48 h,ACAT抑制剂(2μg/ml)和ox-LDL( 50 μg/ml)干预0、6、18、36和48 h,ACAT抑制剂(2μg/ml)、ox-LDL( 50 μg/ml)和不同浓度(0、100、200和400 μmol/L)的牛磺酸熊去氧胆酸(TUDCA)干预48 h.用ELISA法检测细胞上清内脂素的水平,Western印迹法检测脂肪细胞总蛋白GRP78和CHOP表达.ACAT抑制剂和不同浓度的ox-LDL干预脂肪细胞48 h后,随着ox-LDL浓度的增加,脂肪细胞内胆固醇浓度、GRP78和CHOP蛋白表达及内脂素水平显著升高,实验组与空白对照组比较,差异均具有统计学意义(均P＜0.05);ACAT抑制剂和ox-LDL干预后,随干预时间的延长,脂肪细胞GRP78、CHOP蛋白表达及内脂素水平均显著升高,实验组与空白对照组比较,差异均有统计学意义(均P＜0.05);ACAT抑制剂、ox-LDL和不同浓度TUDCA干预48 h后,脂肪细胞GRP78及CHOP蛋白表达水平及内脂素水平逐渐降低,实验组(200和400 μmol/L)与空白对照组比较,差异均有统计学意义(均P＜0.05).脂肪细胞胆固醇负荷增加可促进脂肪细胞分泌内脂素,其机制可能与脂肪细胞的内质网应激增强有关.     

Serum visfatin as a non-traditional biomarker of endothelial dysfunction in chronic kidney disease: an Egyptian study

BackgroundEndothelial dysfunction (ED) is closely linked to cardiovascular disease and outcome in patients with chronic kidney disease (CKD). Visfatin is an adipocytokine that recently generated much interest; however, its role in CKD remains to be clarified. This study aimed to assess visfatin in correlation with markers of ED and inflammation in Egyptian patients with CKD.MethodsThe study included 40 non-diabetic, clinically stable CKD patients and 20 healthy volunteers. Serum levels of visfatin, markers of ED (intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)) and markers of inflammation (interleukin-6 (IL-6), and C-reactive protein (CRP)) were measured. Endothelial function was evaluated using brachial artery flow-mediated dilatation (FMD).ResultsSerum visfatin, ICAM-1, VCAM-1, CRP, and IL-6 levels were significantly elevated and FMD% was decreased in CKD patients as compared to controls. Visfatin correlated positively with ICAM-1, VCAM-1, CRP, and IL-6 and negatively with FMD% in CKD patients. In a multiple regression model, visfatin was strongly and independently associated with FMD (Beta = ?0.02, P < 0.001) in CKD patients.ConclusionsSerum visfatin is strongly associated with endothelial adhesion molecules and FMD%, suggesting that visfatin is an important promising biomarker for prediction of ED and future cardiovascular risk in CKD patients. Moreover, the relationship between visfatin and IL-6 indicates that circulating visfatin may reflect the sub-clinical inflammatory status. Thus, visfatin might be involved in the complex interactions between ED, inflammation, and atherosclerosis and their major clinical consequences; however, further prospective studies are required to prove this hypothesis.     

血浆内脂素浓度与社区获得性肺炎患者预后的相关分析

目的探讨社区获得性肺炎（CAP）患者血浆内脂素浓度对疾病预后的相关价值。方法收集112例健康体检者和112例CAP患者外周血样本,采用酶联免疫吸附试验法检测所有样本血浆内脂素浓度,分析CAP患者血浆内脂素浓度与动脉血氧分压、氧合指数、血白细胞计数、血浆c反应蛋白浓度、肺炎严重指数和急性病生理学和长期健康评价（APACHE）Ⅱ评分的相关程度,并进行Logistic回归分析。采用ROC曲线分析血浆内脂素浓度对CAP患者入院后30d内死亡的预测价值。结果CAP患者血浆内脂素浓度较健康体检者明显增高（t=19．538,P〈0．001）。CAP患者血浆内脂素浓度与动脉血氧分惬（r=-0．451,P〈0．05）、氧合指数（r=-0．473,P〈0．05）、血白细胞计数（r=0．412,P〈0．05）、血浆C-反应蛋白浓度（r=0．501,P〈0．05）、肺炎严重指数（r=0．541,P〈0．05）和APACHEⅡ评分（r=0．528,P〈0．05）均有显著相关。Logistic回归分析显示,血浆内脂素浓度（OR=1．242,95％CI=1．101～2．387,P〈0．001）、肺炎严重指数（OR=1．209,95％CI：1．081,-1．749,P〈0．001）及APACHEⅡ评分（OR=1．368,95％CI=1．107～2．023,P〈0．001）是CAP患者住院后30d内死亡的独立危险因素。ROC曲线分析显示,血浆内脂素浓度对CAP患者住院后30d内死亡有显著预测价值（曲线下面积为0．869,95％CI=0．792．0．925,P〈0．001）。结论内脂素参与社区获得性肺炎的全身炎症反应,血浆内脂素浓度与CAP的预后显著相关。     

妊娠期糖尿病孕妇血清内脂素表达的研究

目的：探讨内脂素(visfatin)与体质量指数(BMI)、血脂[甘油三酯(TG)、总胆固醇(TC)]、胰岛素抵抗(IR)的关系。方法采用电化学发光法和酶联免疫吸附法(ELISA)以及全自动生化仪分别测定52例妊娠期糖尿病孕妇(GDM组)和52例糖耐量正常孕妇(NGT组)的空腹血糖(FPG)、空腹胰岛素(FINS)、visfatin水平。计算BMI和胰岛素抵抗指数(IRI)。结果①GDM组孕妇BMI明显高于NGT组,差异有统计学意义(P<0.05)。②GDM组孕妇TG高于NGT组,差异有统计学意义(P<0.05);两组孕妇TC比较差异无统计学意义(P>0.05)。③GDM组孕妇FPG、FINS、visfatin、IRI均高于NGT组,差异有统计学意义(P<0.05)。结论 GDM孕妇血清visfatin水平明显升高,与机体针对甘油三酯升高和胰岛素抵抗产生的代偿反应有关。     

Plasma visfatin levels in normal weight women with polycystic ovary syndrome

BACKGROUND: The present study was designed to measure plasma visfatin levels in normal weight women with polycystic ovary syndrome (PCOS) and to assess possible correlations between visfatin and the hormonal or metabolic parameters of the syndrome. METHODS: Twenty-five normal weight [body mass index (BMI)<25 kg/m(2)] women with PCOS, 24 obese and overweight (BMI>25 kg/m(2)) controls (ovulating women without clinical or biochemical hyperandrogenism), and 24 normal weight controls were studied. Blood samples were collected between the 3rd and the 7th days of a menstrual cycle in the control groups and during a spontaneous bleeding episode in the PCOS groups at 9:00 A.M., after an overnight fast. Circulating levels of LH, FSH, prolactin (PRL), testosterone (T), Delta(4)-androstenedione (Delta(4)-Alpha), dehydroepiandrosterone sulfate (DHEA-S), 17alpha-OH-progesterone (17OH-P), sex hormone-binding globulin (SHBG), insulin, glucose, and visfatin were measured. RESULTS: Plasma visfatin levels and the visfatin-to-insulin ratio were significantly lower in normal weight controls than in both normal weight women with PCOS and overweight or obese controls. The visfatin-to-insulin ratio was significantly higher in normal weight women with PCOS than in overweight or obese controls. Plasma visfatin levels were found to be positively correlated with LH and Delta(4)A levels, as well as with free androgen index (FAI) values, and negatively correlated with SHBG. LH and SHBG levels were found to be the only independent significant determinants of circulating visfatin. In the control groups, plasma visfatin levels were significantly correlated with BMI, waist (W) measurement, and waist-to-hip ratio (WHR). CONCLUSIONS: Visfatin levels are positively associated with obesity in healthy women of reproductive age. Moreover, the present study indicates, for the first time, a possible involvement of increased visfatin levels in PCOS-associated metabolic and hormonal disturbances.     

内脂素促进巨噬细胞向致血栓表型转化

目的研究内脂素对巨噬细胞中组织因子(TF)和纤溶酶原激活物抑制剂-1(PAI-1)表达的影响及可能的机制。方法体外培养的THP-1细胞中加入不同浓度的内脂素(包括空白对照,50ng/ml,100ng/ml三个浓度组),每组分别孵育6小时,12小时和24小时各3个时间点。同时设立2-羟基萘甲基磷酸三乙酸甲基酯(HNMPA;100umol/L)组。将各组细胞进行realtime PCR和Western blot检测,比较各组TF和PAI-1表达的情况。结果内脂素增加巨噬细胞中TF和PAI-1的mRNA转录和蛋白质表达水平,HNMPA不影响内脂素的这些效应。结论内脂素促进巨噬细胞向促血栓表型转化,机制与胰岛素受体相关的途径无关。